Background: When a passenger suffers an in-flight stroke (IFS), the pilot decides when to expedite access to ground care. Pilot pro-activeness towards IFS could improve outcome and should be promoted. Unfortunately, little is known about a pilot’s stroke pro-activeness or limiting factors. Methods: Randomized controlled trial of an educational intervention (American Stroke Association, 30-slide stroke awareness lecture) through an internet-based computer system using pilot students and instructors as subjects. Pilots completed pre-intervention and post-intervention tests of 25 simulated in-flight scenarios that describe strokes and other neurological and medical symptoms. Outcomes chosen were the percentage of pilots that would use a medical radio service, declare an emergency on board, or divert to the nearest airport for each scenario. Results: Participant pilots (n = 104) were less likely to respond to IFS than to myocardial infarction (p < 0.001). Fear of retaliation by an employer was the most important modifiable limitation. The educational program increased the simulated rate of emergency declarations for in-flight vertebrobasilar strokes (p < 0.001) and subarachnoid hemorrhage (p < 0.001). Conclusions: Pilot-simulated response to certain IFS improves immediately after this educational intervention, which should be disseminated in schools and airlines. Further studies are needed to determine the long-term benefits of this intervention and the impact on actual diversion rates. Companies should also review their policies to shield pilots from retaliation when altering the flight plan for patients.

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